The current invention relates to tablets of low hardness but good physical stability, in particular fast dissolving tablets that can be made at very low compression force, yet have acceptable stability, and methods for preparing such tablets.
Several processes are presently available by which a tablet, which dissolves quickly in the mouth, may be formulated. However, various disadvantages are associated with these currently available methods for producing fast dissolving tablets. For example the addition of high levels of disintegrants is disclosed by Cousin et al. (U.S. Pat. No. 5,464,632). Cousin et al. add two disintegrants to the disclosed tablet formulations, for example 16% starch 1500 and 13.3% crosspovidone. The oral-disintegration time of these tablets is 35 seconds to 45 seconds. However, tablets including high levels of disintegrants have a chalky or dry feel when placed in the mouth.
Another process for producing fast dissolving tablets involves freeze drying or lyophilizing solutions or suspensions of an active ingredient and matrix forming excipients. Pebley et al. (U.S. Pat. No. 5,298,261) disclose freeze-drying a slurry or paste comprising an active ingredient and excipients placed in blister packets. Humbert-Droz et al. (WO 97/36879) disclose vacuum drying, at room temperature or a slightly elevated temperature, a suspension including the active drug, a sugar alcohol, PEG 6000, talc, sweeteners and flavors in preformed blisters. The disadvantages of the freeze drying or vacuum drying methods are time (very slow process), cost of the equipment (not done on conventional tablet manufacturing equipment), and that it is limited to low dose actives.
Fast-dissolving tablets may also be formulated by the inclusion of effervescent coupled compounds. Wehling et al. (U.S. Pat. No. 5,178,878 and WO 91/04757) disclose the addition of an effervescent couple (such as sodium bicarbonate and citric acid) to a tablet. Exposure of the tablet to moisture results in contact and chemical reaction between the effervescent couple which leads to gas production and tablet disintegration. For this reason, tablets which include effervescent pairs are highly sensitive to moisture and have an unpleasant mouthfeel.
Tablets formed by compression under low compression force also dissolve more rapidly than tablets formed by high compression force. However, tablets produced by these processes have a high degree of friability. Crumbling and breakage of tablets prior to ingestion may lead to uncertainty as to the dosage of active ingredient per tablet. Furthermore, high friability also causes tablet breakage leading to waste during factory handling.
The present invention addresses these and other problems associated with the prior art. The invention provides fast-dissolving tablets of low hardness, low friability and high stability which have the added advantage of cost-effective methods of manufacture. In particular, the fast-dissolving tablets of the invention melt rapidly in the mouth and provide an excellent mouth feel.
The present invention advantageously provides compositions and methods for preparing a fast dissolving tablet of low hardness but good physical stability that can be made at very low compression force.
Thus, the invention provides a tablet comprising a low melting point compound that melts or softens at or below 37xc2x0 C., a water soluble excipient, and an active ingredient. Preferably, the low melting point compound comprises from about 2.5% to about 20% (wt/wt) of the composition (e.g., 2.5, 5, 7.5, 10, 12, 14, 16, 18, or 20% (wt/wt)). Preferably the tablet has a hardness of about 3 kP or less, more preferably about 2 kP or less, and still more preferably about 1 kP or less. Preferably, the minimum hardness of the tablet is about 0.1 kP, although lower values, including 0.05 kP, are possible.
The invention further provides a method of producing a tablet composition. The method comprises combining an active agent (also termed xe2x80x9cactive ingredientxe2x80x9d or xe2x80x9cactivexe2x80x9d) with a fast dissolving granulation. The fast dissolving granulation comprises a low melting point compound and a water soluble excipient. Preferably, the low melting compound is present in an amount that will yield values of about 2.5% to about 20% (wt/wt) in a final tablet composition (e.g., 2.5, 5, 7.5, 10, 12, 14, 16, 18, or 20% (wt/wt)).
The accompanying Detailed Description, Examples and Drawings further elaborate the invention and its advantages.